The ability of the somatosensory cortex (SI) to rapidly reorganize after large-scale limb deafferentation has been documented in rat; however the mechanisms underlying this cortical reorganization are not well understood. I propose experiments to determine possible cortical pathways involved in reorganization. These experiments will be followed by a second series where I propose to test whether the perspective pathways actually participate in the reorganization. Two Specific Aims are proposed: Specific Aim 1 Injection of anatomical tracers into physiologically identified sites and intracortical microstimulation (ICMS) will delineate perspective cortical pathways that may play a role in reorganization of SI following large-scale forelimb deafferentation. Studies will be conducted in intact rats. Specific Aim 2 Injection of reversible blocking agents will be made into physiologically identified sites to test the hypothesis that corticocortical pathways participate in large-scale cortical reorganization. Studies will be conducted in adult deafferented rats. The proposed experiments are timely, address testable hypotheses, and the results will lead to a better understanding of the mechanisms underlying cortical plasticity which will be important for treatment of patients suffering from brain injury and stroke.